TY - JOUR
T1 - Genetic analysis of the GABRA1 gene in patients with essential tremor
AU - Deng, Hao
AU - Xie, Wen Jie
AU - Le, Wei Dong
AU - Huang, Mao Sheng
AU - Jankovic, Joseph
N1 - Funding Information:
We are indebted to the participating individuals who made this work feasible. We are grateful to Dr. Guy A. Rouleau's team of the Centre for Research in Neuroscience, McGill University Health Center Research Institute and McGill University, for providing most primer sequences of the GABRA1 gene. Supported by grants NS 043567 and NS 40370 from the National Institute of Neurological Disorders and Stroke.
PY - 2006/6/19
Y1 - 2006/6/19
N2 - The gamma-aminobutyric acid A (GABA-A) receptor mediates inhibitory neurotransmission in the brain and as such may be involved in certain neurological movement disorders, such as tremor. GABA-A receptor alpha 1 (Gabra)-/- mice have been reported to exhibit postural and kinetic, alcohol-responsive, tremor that is characteristic of essential tremor (ET), the most common form of tremor. To determine whether ET is associated with the GABRA1 gene mutation, we screened 76 patients with familial ET and found a novel nucleotide variant: IVS8 + 24 G > T (nt 6119289, NT_023133) in a male patient, and a known 156T > C polymorphism (nt 6090903, NT_023133) in exon 4 in 41% patients, which results in a silent mutation (G52G). No significant association between 156T > C variant and disease risk was found (adjusted OR = 0.95, 95% CI = 0.57-1.61; p = 0.858) by further analysis of 121 familial ET patients and 114 normal controls, except a novel 96A > G (Q32Q; nt 6090743, NT_023133) variant, found in a normal control. Since the 156T > C variant appears to be not pathogenically relevant, our results suggest that missense, nonsense or splice site mutation in the coding region of the GABRA1 gene is not a major genetic cause of ET in Caucasian subjects.
AB - The gamma-aminobutyric acid A (GABA-A) receptor mediates inhibitory neurotransmission in the brain and as such may be involved in certain neurological movement disorders, such as tremor. GABA-A receptor alpha 1 (Gabra)-/- mice have been reported to exhibit postural and kinetic, alcohol-responsive, tremor that is characteristic of essential tremor (ET), the most common form of tremor. To determine whether ET is associated with the GABRA1 gene mutation, we screened 76 patients with familial ET and found a novel nucleotide variant: IVS8 + 24 G > T (nt 6119289, NT_023133) in a male patient, and a known 156T > C polymorphism (nt 6090903, NT_023133) in exon 4 in 41% patients, which results in a silent mutation (G52G). No significant association between 156T > C variant and disease risk was found (adjusted OR = 0.95, 95% CI = 0.57-1.61; p = 0.858) by further analysis of 121 familial ET patients and 114 normal controls, except a novel 96A > G (Q32Q; nt 6090743, NT_023133) variant, found in a normal control. Since the 156T > C variant appears to be not pathogenically relevant, our results suggest that missense, nonsense or splice site mutation in the coding region of the GABRA1 gene is not a major genetic cause of ET in Caucasian subjects.
KW - Essential tremor
KW - GABA-A receptor alpha 1 subunit gene
KW - Genetic analysis
KW - Variant
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U2 - 10.1016/j.neulet.2006.02.066
DO - 10.1016/j.neulet.2006.02.066
M3 - Article
C2 - 16530959
AN - SCOPUS:33646413420
SN - 0304-3940
VL - 401
SP - 16
EP - 19
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1-2
ER -